Fluorescence in situ hybridization identifies high risk Barrett's patients likely to develop esophageal adenocarcinoma

Dis Esophagus. 2016 Aug;29(6):513-9. doi: 10.1111/dote.12372. Epub 2015 Jun 5.

Abstract

Barrett's esophagus (BE) with high-grade dysplasia (HGD) defines a group of individuals at high risk of progression to esophageal adenocarcinoma (EA). Fluorescence in situ hybridization (FISH) has been shown to be useful for the detection of dysplasia and EA in endoscopic brushing specimens from BE patients. The aim of this study was to determine whether FISH in combination with histological findings would further identify more rapid progressors to EA. This is a retrospective cohort study of high-risk patients, having a history of biopsy-confirmed HGD without EA, with an endoscopic brushing specimen analyzed by FISH while undergoing endoscopic surveillance and treatment between April 2003 and October 2010. Brushing specimens were assessed by FISH probes targeting 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) and evaluated for the presence of polysomy, defined as multiple chromosomal gains (displaying ≥ 3 signals for ≥ 2 probes). Specimens containing ≥ 4 cells exhibiting polysomy were considered polysomic. HGD was confirmed by at least two experienced gastrointestinal pathologists. Of 245 patients in this study, 93 (38.0%) had a polysomic FISH result and 152 (62.0%) had a non-polysomic FISH result. Median follow-up was 3.6 years (interquartile range [IQR] 2-5 years). Patients with a polysomic FISH result had a significantly higher risk of developing EA within 2 years (14.2%) compared with patients with a non-polysomic FISH result (1.4%, P < 0.001). These findings suggest that a polysomic FISH result in BE patients with simultaneous HGD identifies patients at a higher risk for developing EA compared with those with non-polysomy.

Keywords: Barrett's esophagus; FISH; cytology; esophageal adenocarcinoma; polysomy.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Aged
  • Barrett Esophagus / genetics*
  • Barrett Esophagus / pathology
  • Cohort Studies
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18 / genetics*
  • DNA Probes
  • Disease Progression
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Esophagoscopy
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence / methods*
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-myc / genetics*
  • Receptor, ErbB-2 / genetics*
  • Retrospective Studies
  • Risk Assessment
  • Trans-Activators / genetics*

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18
  • DNA Probes
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Trans-Activators
  • ZNF217 protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2

Supplementary concepts

  • Adenocarcinoma Of Esophagus